Gonadotropin-releasing hormone (GnRH) is the primary hormone driving all vertebrate reproductive function and is absolutely required for the initiation of pubertal onset. The factors regulating pubertal onset in male mammals are poorly understood, however it is well accepted that gonadal steroid hormones play a prominent role. The recent discovery of estrogen receptors in GnRH neurons suggests the likelihood that estrogen acts directly on the GnRH neuron to modulate its function. The experiments proposed herein will establish: a) the distribution of estrogen receptor beta (ER-beta) and its splice variants in the brain of male mice during sexual maturation; b) if estrogen modulates GnRH promoter activity in vivo and whether this regulation changes across puberty; and c) if estrogen alters GnRH promoter activity through ER-beta or its splice variants in vitro. Overall these studies will provide important information about the mechanisms regulating puberty in male mammals. [unreadable] [unreadable]